We are reflecting on the top 10 advances in oncology throughout 2017.
Welcome to OncLive News Network! I’m Gina Columbus.
First up, the FDA granted an accelerated approval in May to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient solid tumors that have progressed after prior treatment and who have no satisfactory alternative treatment options. Pembrolizumab was also indicated for patients with MSI-H or dMMR colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.
The approval was the first for the cancer community, as this was the first time a drug was approved based on a tumor’s biomarker without regard to the tumor’s original location.
The approval was based on data from 149 patients with MSI-H or dMMR cancers enrolled across 5 single-arm clinical trials. Results showed that the objective response rate with pembrolizumab was 39.6%, including 11 complete responses and 48 partial responses. The ORR was 36% in patients with CRC and 46% in patients with other tumor types.
2017 also included the 2 first chimeric antigen receptor T-cell therapy approvals. In August, the FDA authorized the use of tisagenlecleucel for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.
The primary efficacy analysis was based on phase II results from the single-arm, international ELIANA trial, which demonstrated an overall remission rate of 82.5% in treated subjects. Forty patients had complete remission and 12 had complete remission with incomplete hematologic recovery.
The second FDA approval came in August for the CD19-directed CAR T-cell therapy axicabtagene ciloleucel as a treatment for adults with relapsed or refractory non-Hodgkin lymphoma. The decision was based on complete remission rates in the phase II ZUMA-1 trial, which demonstrated an ORR of 82% and a CR rate of 54%.
In May, the FDA approved the first immunotherapy and chemotherapy combination with pembrolizumab plus pemetrexed and carboplatin as a frontline treatment for patients with metastatic or advanced nonsquamous non—small cell lung cancer, regardless of PD-L1 expression.
The decision was based on part 2 of cohort G in the phase II KEYNOTE-021 trial, in which the pembrolizumab triplet elicited an objective response rate of 55% versus 29% with the chemotherapy agents alone. The median progression-free survival was 13.0 months with the addition of pembrolizumab versus 8.9 months for chemotherapy alone.
The frontline setting for ALK-positive non—small cell lung cancer changed dramatically with the November FDA approval of alectinib, a second-generation ALK inhibitor.
The frontline approval is primarily based on findings from the phase III ALEX study. Here, results showed that alectinib improved progression-free survival by 47% versus the standard of care, crizotinib.
In addition to granting this new indication, the FDA has also converted alectinib’s accelerated approval for patients with ALK-positive NSCLC who have progressed on crizotinib to a full approval.
Additional lung cancer studies had practice-changing results in 2017. The phase III FLAURA trial, which explored osimertinib in the first-line setting for patients with EGFR-mutant non—small cell lung cancer versus standard tyrosine kinase inhibitors, including erlotinib and gefitinib, showed a significant improvement in progression-free survival.
Results showed that the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib. Based on these findings, osimertinib was recently granted a priority review designation by the FDA for the frontline indication.
Secondly, for patients with stage III NSCLC who have received treatment with chemotherapy and radiation, durvalumab also improved PFS over placebo in the phase III PACIFIC study. The median PFS was 16.8 months with durvalumab versus 5.6 months for placebo.
Ten years after having no new agents approved in the liver cancer landscape, regorafenib and nivolumab were granted approval by the FDA as second-line therapies for patients who have progressed on sorafenib.
Regorafenib was approved in April, followed by nivolumab’s indication in September 2017.
The approval of regorafenib is based on the phase III RESORCE trial, in which the median overall survival was 10.6 months with regorafenib plus best supportive care compared with 7.8 months for placebo plus best supportive care, representing a 38% reduction in the risk of death.
Nivolumab’s approval is based on data from the phase I/II CheckMate-040 trial, in which the overall response rate by blinded independent central review was 18.2% per mRECIST criteria for patients who had previously been treated with sorafenib.
Four checkpoint inhibitors, plus 1 new indication, were approved in the space of bladder cancer this year.
Beginning in February, the PD-1 inhibitor nivolumab was approved for patients with locally advanced or metastatic disease that progressed during or after platinum-based chemotherapy, or less than 12 months of receiving platinum-containing chemotherapy, either before or after surgery.
In April, the FDA granted an accelerated approval to atezolizumab as a frontline treatment for cisplatin-ineligible patients with locally advanced or metastatic disease. Atezolizumab was previously approved in 2016 in the second-line setting.
In May, durvalumab, a PD-L1 inhibitor, was granted approval for patients whose disease progressed during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Later that same month, avelumab, another PD-L1 inhibitor, was granted approval for the same indication.
But it was pembrolizumab that was granted 2 indications by the FDA in May. It was not only granted in the second-line space, but also as a frontline regimen for patients who are ineligible to receive cisplatin-containing chemotherapy.
In breast cancer, two CDK4/6 inhibitors were added to the armamentarium this year.
In March, the FDA approved ribociclib for use in combination with an aromatase inhibitor for the frontline treatment of postmenopausal women with hormone-receptor—positive, HER2-negative advanced breast cancer.
Ribociclib’s approval is based on findings from the phase III MONALEESA-2 trial, in which combining ribociclib with letrozole reduced the risk of progression or death by 44% versus letrozole alone in this setting.
Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer with disease progression following endocrine therapy was approved by the FDA in September. The CDK4/6 inhibitor was also approved as a monotherapy for patients with HR+/HER2- breast cancer with metastatic disease who have previously received endocrine therapy and chemotherapy.
In melanoma, the FDA awarded the combination of dabrafenib and trametinib a breakthrough therapy designation for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection.
If approved, the combination would be the first adjuvant treatment specifically aimed at this patient population. The decision was based on findings from the COMBI-AD study, which demonstrated that the 3-year overall survival in this population was 86% versus 77% favoring the combination arm.
Another adjuvant combination regimen in melanoma had exciting results this year. The combination of adjuvant nivolumab and ipilimumab led to a 3-year relapse-free survival rate of 71% in patients with high-risk resected stage IIIC/IV melanoma.
Finally, our tenth advancement in the oncology field are the first FDA approvals of biosimilars.
In September, ABP-215, a biosimilar for bevacizumab developed by Amgen and Allergan, was approved for the treatment of patients with colorectal, lung, brain, kidney, and cervical cancers in adult patients.
The FDA approved the trastuzumab biosimilar MYL-1401O in December for HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma, the same indications as trastuzumab.
That’s all for today and for 2017. We now look forward to next year’s major advances.
Thank you for watching OncLive News Network! I’m Gina Columbus.